A Novel Mouse Model of Prenatal Opioid Exposure

产前阿片类药物暴露的新型小鼠模型

基本信息

批准号：
10373004
负责人：
DEVON L GRAHAM
金额：
$ 7.7万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10373004
关键词：
12 year old Adolescent Adult Adult Children Affect Age American Anxiety Applications Grants Area Attention Behavior Behavioral Birth Brain Cardiopulmonary Child Childhood Clinical Pharmacology Clinical Research Cognition Communities Congenital Abnormality Data Development Disease Dose Drug Addiction Drug Kinetics Epidemic Exhibits Exposure to Family Female Female of child bearing age Fentanyl Fetal Growth Fetus Future Goals Health Healthcare Industry Heart Rate Heroin Human In Vitro Individual Infant Intravenous Lead Learning Liver Long-Term Effects Maternal Behavior Maternal-Fetal Exchange Measurement Measures Memory Modeling Modification Morphine Motor Mus Neonatal Neonatal Abstinence Syndrome Neurobiology Opioid Opioid agonist Oral Administration Outcome Pattern Performance Perinatal Pharmaceutical Preparations Pharmacology Phenotype Physiological Placenta Plasma Population Positioning Attribute Pregnancy Pregnant Women Prevalence Property Research Rodent Model Route Schools Signal Transduction Social Behavior Social Interaction Social outcome Source Testing Therapeutic Time Treatment Protocols Withdrawal Withdrawal Symptom addiction analog base behavior observation behavioral outcome clinically relevant drug of abuse drug reward exposed human population exposure route fetal fetal opioid exposure functional outcomes in utero male maternal opioid use medication-assisted treatment mouse model mu opioid receptors negative affect neonate neural circuit neurobehavioral neuronal circuitry next generation novel offspring opioid abuse opioid exposure opioid misuse opioid use overdose death perinatal period pre-clinical pregnant prenatal prenatal exposure prescription opioid receptor relating to nervous system social synthetic opioid

项目摘要

PROJECT SUMMARY/ABSTRACT Opioid use within the US has reached epidemic proportions, negatively impacting not just individuals and their families, but also communities. One of the most affected populations is pregnant women and their exposed offspring. Despite efforts to reduce access to prescription opioids, more potent, synthetic analogs such as fentanyl are becoming more readily available. Little is known of the long-term effects of fentanyl in exposed children. In this proposal, we will develop a clinically relevant mouse model of prenatal fentanyl exposure to determine the pharmacokinetic and functional (behavioral) profiles in exposed offspring. Developmental opioids are known to affect specific behavioral domains, and we will test offspring at both early (neonatal) and late (adult) ages. We hypothesize that fentanyl will diminish performance of behaviors related to drug reward and addiction, cognition, affect, social outcomes, and motor coordination. We further posit that the route and duration of exposure will exacerbate these deficiencies. This study will be the first to examine how long-term developmental fentanyl exposure alters both short- and long-term functional outcomes and will position us to determine the critical neural circuit changes underlying these altered phenotypes in order to develop therapeutic approaches in exposed children

项目摘要/摘要美国境内的阿片类药物使用已达到流行比例，不仅对个人及其家庭，也是社区。受影响最大的人群之一是孕妇及其暴露后代。尽管努力减少使用处方阿片类药物的机会，但更有效的合成类似物，例如芬太尼变得越来越容易获得。芬太尼在暴露中的长期作用知之甚少孩子们。在此提案中，我们将开发出临床上相关的小鼠芬太尼暴露于确定暴露后代的药代动力学和功能（行为）谱。发展已知阿片类药物会影响特定的行为领域，我们将在早期（新生儿）和迟到（成人）年龄。我们假设芬太尼会降低与药物奖励相关的行为的表现以及成瘾，认知，情感，社会成果和运动协调。我们进一步认为路线和暴露持续时间会加剧这些缺陷。这项研究将是第一个研究长期的研究发展性芬太尼暴露会改变短期和长期功能结果，并将我们定位为确定这些改变的表型的关键神经回路变化以发展暴露儿童的治疗方法